Design, synthesis and evaluation of amino-substituted 1H-phenalen-1-ones as anti-leishmanial agents

Design, synthesis and evaluation of amino-substituted 1H-phenalen-1-ones as anti-leishmanial agents
Freijo, Mónica Blanco; López-Arencibia, Atteneri; Piñero, José E.; McNaughton-Smith, Grant; Abad-Grillo, Teresa
2018-01-01 00:00:00
Screening of a designed collection of mono-substituted amino-1H-phenalen-1-ones against promastigote forms of L. donovani and L. amazonensis, identified seven compounds with anti-leishmanial activities comparable or better than the commonly prescribed anti-leishmanial drug, miltefosine. Structure-activity analysis revealed that appendages containing a basic tertiary nitrogen were favored, and that the position of the appendage also affected their potency. Like miltefosine, several of these active compounds significantly reduced the mitochondrial membrane potential in promastigotes. Further studies in amastigotes of L. amazonensis revealed that compounds 14, 15 and 33 were more active and more selective than miltefosine, with sub-micromolar potencies and selectivity indices >100.
http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.pngEuropean Journal of Medicinal ChemistryElsevierhttp://www.deepdyve.com/lp/elsevier/design-synthesis-and-evaluation-of-amino-substituted-1h-phenalen-1-2mgy3N2A4I

Design, synthesis and evaluation of amino-substituted 1H-phenalen-1-ones as anti-leishmanial agents

Abstract

Screening of a designed collection of mono-substituted amino-1H-phenalen-1-ones against promastigote forms of L. donovani and L. amazonensis, identified seven compounds with anti-leishmanial activities comparable or better than the commonly prescribed anti-leishmanial drug, miltefosine. Structure-activity analysis revealed that appendages containing a basic tertiary nitrogen were favored, and that the position of the appendage also affected their potency. Like miltefosine, several of these active compounds significantly reduced the mitochondrial membrane potential in promastigotes. Further studies in amastigotes of L. amazonensis revealed that compounds 14, 15 and 33 were more active and more selective than miltefosine, with sub-micromolar potencies and selectivity indices >100.

Journal

European Journal of Medicinal Chemistry
– Elsevier

Published: Jan 1, 2018

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References

Infectious diseases: Leishmaniasis

Croft, S.L.

Visceral leishmaniasis: what are the needs for diagnosis, treatment and control?